Identification of outliers in gene expression data

Abstract:

This work reports the application of techniques that proved useful in analyzing a large
gene expression data set. Because it appears likely that genomic instability in cancers can
optimize gene expression for cell growth, the differences between normal and tumor expression
patterns might help us understand what is being selected for as cancerous tissues evolve.
Molecular heterogeneity of cancer, caused by various gene mutations, can yield extensive
heterogeneity in gene expression profile in cancer samples. To detect cancer-related genes which
are active only in a subset of cancer samples or cancer outliers, recently, Tomlins et al. (2005)
argued that traditional analytical methods, for example, a two-sample t-statistic, which search for
common activation of genes across a class of cancer samples, will fail to detect cancer genes
which show differential expression in a subset of cancer samples or cancer outliers. They
developed the “cancer outlier profile analysis” (COPA) method to detect cancer genes with such
heterogeneous expression profiles within cancer samples and revealed subtypes of prostate
cancer patients defined by recurrent chromosomal aberration. Inspired by the COPA statistic,
some authors have proposed other methods for detecting cancer-related genes with cancer outlier
profiles in the framework of multiple testing (Tibshirani-2007, Wu-2007, Lian-2008, Wang-
2010). Such cancer outlier analyses are affected from many problems specially if there is any
outlier in the data set then classical measures of location and scale are seriously affected. So the
test statistic using these parameters might not be appropriate to detect outliers. In this study, we
try to robustify some existing methods. We propose three new techniques Expressed robust tstatistic
(ERT), Modified Outlier robust t-statistic (MORT) and Least Sum Square of Ordered
Subset Robust t-statistic (LSOSRT) for the identification of outliers. The usefulness of the
proposed methods is then investigated by Monte Carlo simulation and real cancer data. We find
our new methods efficient.